title: Alantolactone inhibits cell proliferation by interrupting the interaction between Cripto-1 and activin receptor type II A in activin signaling pathway.
abstract: It has been suggested that deregulation of activin signaling contributes to tumor formation. Activin signaling is blocked in cancer cells due to the complex formed by Cripto-1, activin, and activin receptor type II (ActRII). In this study, the authors used a mammalian two-hybrid system to construct a drug screening model to obtain a small molecular inhibitor capable of interrupting the interaction between Cripto-1 and ActRII. They screened 300 natural components and identified alantolactone. Data suggested that alantolactone induced activin/SMAD3 signaling in human colon adenocarcinoma HCT-8 cells. The authors also found that alantolactone exhibited antiproliferative function specific to tumor cells, with almost no toxicity to normal cells at a concentration of 5 µg/mL. Furthermore, they proved that the antiproliferative function of alantolactone was activin/SMAD3 dependent. These results suggest that alantolactone performs its antitumor effect by interrupting the interaction between Cripto-1 and the activin receptor type IIA in the activin signaling pathway. Moreover, screening for inhibitors of Cripto-1/ActRII is a potentially beneficial approach to aid in discovering novel cancer treatment.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Yong Li
authors.initials: YL
authors.lastname: Bao
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.forename: Chun Lei
authors.initials: CL
authors.lastname: Yu
authors.forename: Yan Xin
authors.initials: YX
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Li Hua
authors.initials: LH
authors.lastname: Zheng
authors.forename: Yu Xin
authors.initials: YX
authors.lastname: Li
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism*; D028341:Activins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D058851:GPI-Linked Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D045787:Sesquiterpenes, Eudesmane / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007783:Lactones; D009363:Neoplasm Proteins; D045787:Sesquiterpenes, Eudesmane; D054852:Small Molecule Libraries; C070636:TDGF1 protein, human; D028341:Activins; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A; C004363:alantolactone